Magnetic Resonance Imaging-Based Delineation of Organs at Risk in the Head and Neck Region.

Purpose: The aim of this article is to establish a comprehensive contouring guideline for treatment planning using only magnetic resonance images through an up-to-date set of organs at risk (OARs), recommended organ boundaries, and relevant suggestions for the magnetic resonance imaging (MRI)-based delineation of OARs in the head and neck (H&N) region. Methods and Materials: After a detailed review of the literature, MRI data were collected from the H&N region of healthy volunteers. OARs were delineated in the axial, coronal, and sagittal planes on T2-weighted sequences. Every contour defined was revised by 4 radiation oncologists and subsequently by 2 independent senior experts (H&N radiation oncologist and radiologist). After revision, the final structures were presented to the consortium partners. Results: A definitive consensus was reached after multi-institutional review. On that basis, we provided a detailed anatomic and functional description and specific MRI characteristics of the OARs. Conclusions: In the era of precision radiation therapy, the need for well-built, straightforward contouring guidelines is on the rise. Precise, uniform, delineation-based, automated OAR segmentation on MRI may lead to increased accuracy in terms of organ boundaries and analysis of dose-dependent sequelae for an adequate definition of normal tissue complication probability.

Low Fraction Size Re-irradiation for Large Volume Recurrence of Glial Tumours.

The aim of the present study was to evaluate the efficacy of re-irradiation (re-RT) in patients with advanced local relapses of glial tumours and to define the factors influencing the result of the hyper-fractionated external beam therapy on progression after primary management. We have analysed the data of 55 patients with brain tumours (GBM: 28) on progression, who were re-irradiated between January 2007 and December 2018. The mean volume of the recurrent tumour was 118 cm3, and the mean planning target volume (PTV) was 316 cm3, to which 32 Gy was delivered in 20 fractions at least 7.7 months after the first radiotherapy, using 3D conformal radiotherapy (CRT) or intensity modulated radiotherapy (IMRT). The median overall survival (mOS) from the re-RT was 8.4 months, and the 6-month and the 12-month OS rate was 64% and 31%, respectively. The most important factors by univariate analysis, which significantly improved the outcome of re-RT were the longer time interval between the diagnosis and second radiotherapy (p = 0.029), the lower histology grade (p = 0.034), volume of the recurrent tumour (p = 0.006) and Karnofsky performance status (KPS) (p = 0.009) at the re-irradiation. Our low fraction size re-irradiation ≥ 8 months after the first radiotherapy proved to be safe and beneficial for patients with large volume recurrent glial tumours.

Boost Irradiation Integrated to Whole Brain Radiotherapy in the Management of Brain Metastases.

Our retrospective analysis aimed to evaluate the clinical value of dose intensification schemes: WBRT and consecutive, delayed, or simultaneous integrated boost (SIB) in brain metastasis (BM) management. Clinical data and overall survival (OS) of 468 patients with BM from various primaries treated with 10 × 3 Gy WBRT (n = 195), WBRT+ 10 × 2 Gy boost (n = 125), or simultaneously 15 × 2.2 Gy WBRT+0.7 Gy boost (n = 148) during a 6-year period were statistically analysed. Significant difference in OS could be detected with additional boost to WBRT (3.3 versus 6.5 months) and this difference was confirmed for BMs of lung cancer and melanoma and both for oligo- and multiplex lesions. The OS was prolonged for the RPA 2 and RPA3 categories, if patients received escalated dose, 4.0 vs. 7.7 months; (p = 0.002) in class RPA2 and 2.6 vs. 4.2 months; (p < 0.0001) in the class RPA 3 respectively. The significant difference in OS was also achieved with SIB. The shortened overall treatment time of SIB with lower WBRT fraction dose exhibited survival benefit over WBRT alone, and could be applied for patients developing BM even with unfavourable prognostic factors. These results warrant for further study of this approach with dose escalation using the lately available solutions for hippocampus sparing and fractionated stereotactic irradiation. The simultaneous delivery of WBRT with reduced fraction dose and boost proved to be advantageous prolonging the OS with shortened treatment time and reduced probability for cognitive decline development even for patients with poor performance status and progressing extracranial disease.

Prone Positioning on a Belly Board Decreases Rectal and Bowel Doses in Pelvic Intensity-Modulated Radiation Therapy (IMRT) for Prostate Cancer.

The presence of normal tissues in the irradiated volume limits dose escalation during pelvic radiotherapy (RT) for prostate cancer. Supine and prone positions on a belly board were compared by analyzing the exposure of organs at risk (OARs) using intensity modulated RT (IMRT). The prospective trial included 55 high risk, localized or locally advanced prostate cancer patients, receiving definitive image-guided RT. Computed tomography scanning for irradiation planning was carried out in both positions. Gross tumor volume, clinical and planning target volumes (PTV) and OARs were delineated, defining subprostatic and periprostatic rectal subsegments. At the height of the largest antero-posterior (AP) diameter of the prostate, rectal diameters and distance from the posterior prostate wall were measured. IMRT plans were generated. Normal tissue exposure and structure volumes were compared between supine and prone plans using paired t-test. In the volumes of the prostate, PTV, colon and small bowel, no significant differences were found. In prone position, all rectal volumes, diameters, and rectum-prostate distance were significantly higher, the irradiated colon and small bowel volume was lower in dose ranges of 20-40 Gy, and the exposure to all rectal segments was more favorable in 40-75 Gy dose ranges. No significant difference was found in the exposure of other OARs. Prone positioning on a belly board is an appropriate positioning method aiming rectum and bowel protection during pelvic IMRT of prostate cancer. The relative reduction in rectal exposure might be a consequence of the slight departure between the prostate and rectal wall.

Clinical benefit of fulvestrant monotherapy in the multimodal treatment of hormone receptor and HER2 positive advanced breast cancer: a case series.

Fulvestrant is a pure estrogen receptor (ER) antagonist approved for the treatment of metastatic ER positive breast cancer in postmenopausal women with disease progression following antiestrogen therapy. The clinical results of fulvestrant demonstrated encouraging activity in tumors in spite of HER2 positivity, but data about its use after progression on anti-HER2 agents are limited. Partial responses and durations of response of 12, 25, and 38 months in three cases with multiple metastases of ER positive and HER2 positive breast cancer were observed; all patients had been treated with 1-4 regimens of an anti-HER2 agent in combination with chemotherapy or an aromatase inhibitor before the initiation of fulvestrant. Fulvestrant is a valuable option with limited toxicity and durable response in metastatic HER2 and ER positive breast cancer after progression on anti-HER2 agents as well. Therapeutic benefit even in extensive skin metastases and (irradiated) brain metastases may be expected. Further investigations are warranted to establish where it fits into the multimodal management of ER and HER positive breast cancer.

Daily Setup Accuracy, Side-effects and Quality of Life During and After Prone Positioned Prostate Radiotherapy.

BACKGROUND/AIM: Exposure of organs at risk with prostate radiotherapy (RT) is lower in the prone position. This study is a prospective evaluation of setup accuracy, side-effects, and quality of life (QOL) during and after prone positioned RT. PATIENTS AND METHODS: Image-guided (IG) intensity-modulated (IM) RT was administered in prone position on belly-board to 55 high-risk prostate cancer (PC) patients. Rectum diameters were measured in two areas of the symphysis at the beginning of RT and during it. Side-effects, QOL, and prostate specific symptoms (PSS) were evaluated. RESULTS: Setup accuracy was similar to that reported in the literature. In the upper area of symphysis rectal diameters were significantly changed during treatment, but in the prostate region, no difference was detected. No change was detected in patients' QOL and PSS during treatment, but after RT, they improved. CONCLUSION: Prone positioned IG-IMRT is feasible with tolerable side-effects for high-risk PC patients. Changes in QOL and PSS are insignificant during RT, while improvement after RT suggests a rapid recovery.

Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR).

The embryonal tumor with abundant neuropil and true rosettes is a rare and highly malignant variant of embryonal brain tumors. It usually affects infants and young children under the age of 4 years and exhibits a very aggressive course with a dismal prognosis. For the 68 cases reported to date the mean age at diagnosis was 25.42 months (range 3-57 months). Survival data are available for 48 children (including our case): the median overall survival is 13.0 months, though 6 (9%) of the children have had a relative long survival (>30 months). The aggressive combined treatment, involving primary surgical tumor removal, adjuvant polychemotherapy, including high-dose chemotherapy with stem cell transplantation, radiotherapy and radiochemotherapy, might play an important role in the longer survival. We have performed a literature review and we present here a multimodal-treated case of a 2- year-old girl with a long survival, who was reoperated when recurrence occurred. The residual tumor demonstrated a good response to temozolomide radiochemotherapy (craniospinal axis + boost) and followed by maintenance temozolomide. The described complex aggressive treatment option might be considered for future cases of this tumor entity.

[Role of 18FDG-PET/CT in the management and gross tumor volume definition for radiotherapy of head and neck cancer; single institution experiences based on long-term follow-up]. / 18FDG-PET/CT szerepe fej-nyak daganatok kezelésében és a sugárterápiás tumortérfogat meghatározásában - Az SZTE Onkoterápiás Klinika eredményeinek értékelése.

The purpose of our work is evaluation of the impact of 18FDG-PET/CT on the complex management of locoregionally advanced (T3-4N1-3) head and neck squamous cell cancer (LAHNSC), and on the target definition for 3D conformal (3DCRT) and intensity-modulated radiotherapy (IMRT). 18FDG-PET/CT were performed on 185 patients with LAHNSC prior to radiotherapy/chemoradiation in the treatment position between 2006 and 2011. Prior to it 91 patients received induction chemotherapy (in 20 cases of these, baseline PET/CT was also available). The independently delineated CT-based gross tumor volume (GTVct) and PET/CT based ones (GTVpet) were compared. Impact of PET/CT on the treatment strategy, on tumor response evaluation to ICT, on GTV definition furthermore on overall and disease-specific survival (OS, DSS) was analysed. PET/CT revealed 10 head and neck, 2 lung cancers for 15 patients with carcinoma of unknown primary (CUP) while 3 remained unknown. Second tumors were detected in 8 (4.4%), distant metastasis in 15 (8.2%) cases. The difference between GTVct and GTVpet was significant (p=0.001). In 16 patients (14%) the GTVpet were larger than GTVct due to multifocal manifestations in the laryngo-pharyngeal regions (4 cases) or lymph node metastases (12 cases). In the majority of the cases (82 pts, 72%) PET/CT-based conturing resulted in remarkable decrease in the volume (15-20%: 4 cases, 20-50%: 46 cases, >50%: 32 cases). On the basis of the initial and post-ICT PET/CT comparison in 15/20 patients more than 50% volume reduction and in 6/20 cases complete response were achieved. After an average of 6.4 years of follow-up the OS (median: 18.3±2.6 months) and DSS (median: 25.0±4.0 months) exhibited close correlation (p=0.0001) to the GTVpet. In cases with GTVpet <10 cm3 prior to RT, DSS did not reach the median, the mean is 82.1±6.1 months, while in cases with GTVpet 10-40 cm3 the median of the DSS was 28.8±4.9 months (HR = 3.57; 95% CI: 1.5-8.3), and in those with GTVpet >40 cm3 the median DSS was 8.4±0.96 months (HR= 11.48; 95% CI: 5.3-24.9). Our results suggest that 18FDG-PET/CT plays an important role for patient with LAHNSC, by modifying the treatment concept and improving the target definition for selective RT modalities. Volumetric PET/CT-based assessment of the tumor response after ICT gives valuable contribution to further therapy planning.

Clinical course of central neurocytoma with malignant transformation-an indication for craniospinal irradiation.

Central neurocytoma is generally considered to be a benign tumor and the literature suggests that a cure may be attained by surgery ± adjuvant focal irradiation. However, there is a need for change in the therapeutic strategy for the subgroup of patients with aggressive central neurocytoma. An example case is presented and the literature on central neurocytoma cases with malignant features and dissemination via the cerebrospinal fluid is reviewed and the radiotherapeutic strategies available for central neurocytoma treatment is discussed. Nineteen cases including the present report with a malignant course and cerebrospinal fluid dissemination have been described to date, most of them involving an elevated MIB-1 labeling index. Our case exhibited atypical central neurocytoma with an initially elevated MIB-1 labeling index (25-30 %). The primary treatment included surgery and focal radiotherapy. Three years later the disease had disseminated throughout the craniospinal axis. A good tumor response and symptom relief were achieved with repeated radiation and temozolomide chemotherapy. Central neurocytoma with an initially high proliferation activity has a high tendency to spread via the cerebrospinal fluid. The chemo- and radiosensitivity of the tumor suggest a more aggressive adjuvant therapy approach. Cases with a potential for malignant transformation should be identified and treated appropriately, including irradiation of the entire neuroaxis and adjuvant chemotherapy may be considered.